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Powering Membrane Traffic in Endocytosis and Recycling

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Powering Membrane Traffic in Endocytosis and Recycling REVIEWS Powering membrane traffic in endocytosis and recycling Thierry Soldati* and Manfred Schliwa‡ Abstract | Early in evolution, the diversification of membrane-bound compartments that characterize eukaryotic cells was accompanied by the elaboration of molecular machineries that mediate intercompartmental communication and deliver materials to specific destinations. Molecular motors that move on tracks of actin filaments or microtubules mediate the movement of organelles and transport between compartments. The subjects of this review are the motors that power the transport steps along the endocytic and recycling pathways, their modes of attachment to cargo and their regulation. Endocytosis The emergence of eukaryotic cells was accompanied by attempt to consider details of the secretory pathway nor A plasma-membrane- the development of endomembrane systems that com- trafficking related to other organelles such as mitochon- associated process in which a partmentalize biochemical pathways and biosynthetic dria, chloroplasts or peroxisomes. We follow the journey eukaryotic cell engulfs processes. An evolutionary trend towards increasing of endocytic compartments on their inbound route from extracellular fluid or particles. complexity and subcellular specialization necessitated the plasma membrane to their centrally located destina- Phagocytosis the development of machineries for intercompartmental tions and then accompany recycling compartments back A form of endocytosis in which communication. Molecular assemblies evolved to con- to the surface. Most of the data referred to have been a eukaryotic cell engulfs large fer specificity to the interactions of donor and acceptor acquired from animal systems, except where mentioned particles, such as bacteria. compartments (budding, sorting, tethering and fusion). otherwise. The basic properties of molecular motors, Pinocytosis Cytoskeletal polymers such as actin filaments and such as how they generate movement and tension, have 1 A form of endocytosis in which microtubules, which help segregate genetic material and been discussed in a compilation of reviews elsewhere , a eukaryotic cell engulfs determine cell shape and subcellular architecture, were although some of the salient features are summarized in extracellular fluid and solutes. co-opted as tracks for transport. In animal cells, micro- BOX 1. For a discussion of the additional mechanisms by tubules support long-range transport, whereas the more which motors produce movement, such as harnessing Macropinocytosis A form of pinocytosis, flexible actin filaments serve short-range movements the power of actin polymerization, readers are referred 2,3 morphologically and both near the cell periphery and in the cell interior. Also, to recent reviews . The diversity of the motors that are mechanistically related to actin filaments can be woven into dense networks of short engaged in these processes is reflected in the complexity phagocytosis, by which cells fibres through the action of crosslinkers and branch- of attachment modes to their diverse cargoes, which are form large membrane vesicles. promoting complexes. On the other hand, in many plant summarized in BOX 2. More complete outlines of cargo- cells, bundled actin filaments can form extended tracks binding mechanisms can be found in recent reviews4–6. for long-distance transport. Owing to the gel-like nature Here, we emphasize the interplay between endocytic *Départment de Biochimie, of the cytoplasm, the Brownian movement of organelles is and recycling traffic, and the requirement for molecular Faculté des Sciences, severely restricted and cargoes have to be transported to motors in these dynamic processes. Université de Genève, 30 quai Ernest Ansermet, Sciences II, their destinations at the expense of energy. Furthermore, CH-1211-Genève-4, seemingly random, but motor-dependent, movement is Inbound traffic Switzerland. proposed to increase the probability of vesicle collisions Endocytosis probably evolved as a process to take up ‡Institute for Cell Biology, and therefore promote fusion events. Movement is pow- nutrients from the environment and to avoid the University of Munich, ered by three ATP-dependent motors: myosin, kinesin need to secrete hydrolytic enzymes for the purpose of Schillerstr. 42, D-80336 Munich, Germany. and dynein. Over the course of eukaryotic evolution, extra cellular digestion. Endocytosis can be divided e-mails: these motors have diversified into a large number of into phagocytosis, which is the uptake of particles, and thierry.soldati@biochem. families with specific tasks (FIG. 1). pinocytosis, which is the uptake of fluid. Depending on unige.ch; schliwa@med. Here, we review the involvement of molecular motors the type of particle and the receptors that are required, uni-muenchen.de doi:10.1038/nrm1960 in the movement of endosomes and in vesicular traffick- several morpho logical and functional modes of phago- Published online ing along the endocytic and recycling pathways. These cytic uptake have been described. Furthermore, there are 8 November 2006 pathways are summarized in FIG. 2. We do not, however, four basic mechanisms for pinocytosis: macropinocytosis, NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 7 | DECEMBER 2006 | 897 © 2006 Nature Publishing Group REVIEWS a Myosin motors Myo I Basic SH3 Myo II Myo III Kinase Myo IV MyTH4 SH3 Myo V Myo VI Minus-end directed Myo VII MyTH4FERMSH3 MyTH4 FERM Myo VIII Myo IX RhoGAP Myo X PH PH PH MyTH4 FERM Myo XI Myo XII MyTH4 MyTH4 FERM Myo XIII Basic Myo XIV Basic Myo XV MyTH4FERMSH3 MyTH4 FERM Myo XVI AAAAAAAA Proline-rich Myo XVII Chitin synthase Myo XVIII PDZ b Microtubule motors Kinesin-1 (conventional) Kinesin-2 (KRP85/95) Kinesin-3 (UNC104) FH PH Kinesin-4 (chromokinesin) Kinesin-5 (BIMC) Kinesin-6 (MKLP) Kinesin-7 (CENP-E) Kinesin-8 (KIP3) Kinesin-13 (MCAK) Kinesin-14 (C-terminal) Minus-end directed c Dynein motors Dynein (cytoplasmic) HC/IC AAA1 AAA2 AAA3AAA4M AAA5 AAA6 Motor families involved in membrane trafficking Motor families with some members involved in membrane trafficking Myosin families of plants with members involved in membrane trafficking Motor domain PH Pleckstrin-homology domain N-terminal domain (functions are largely unknown) AAA Ankyrin repeats IQ-motifs (light-chain-binding domains) PDZ PDZ domain Tail region, non-homologous FH Forkhead-associated domain Coiled-coil domain (oen interrupted) HC/IC Heavy chain–intermediate chain interaction domain SH3 SRC-homology-3 domain AAA Triple A-domain (ATPase associated with various activities) MyTH4 Myosin tail-homology-4 domain M Microtubule interaction site FERM Protein 4.1, ezrin, radixin, moesin domain Region encompassing the stalk 898 | DECEMBER 2006 | VOLUME 7 www.nature.com/reviews/molcellbio © 2006 Nature Publishing Group REVIEWS Clathrin-mediated clathrin-mediated endocytosis, caveolae-mediated endocytosis to myosin Ic, supports a role for both of these myosins endocytosis and at least one less well-defined clathrin- and caveolae- in anchoring the plasma membrane to the underlying A form of pinocytosis, often independent endocytosis pathway. Recent reviews describe actin cytoskeleton19. also referred to as receptor- these portals of entry into the cell in detail7,8. Following internalization, myosin V probably con- mediated endocytosis, in which trols short-range phagosome movement and delivers the invagination of the endocytic vesicle is driven by Phagocytosis. Phagocytosis involves the active pro- phagosomes to the microtubule system for transport the clathrin coat. trusion of lamellipodia around an object that is to be mostly (but not exclusively) in the minus-end direction20 engulfed, and several myosin classes are involved in (discussed below). Caveolae-mediated this process. Myosin Ic9 and myosin X10 seem to be key endocytosis A form of pinocytosis that is players in the extension of phagocytic cup pseudopods, Macropinocytosis. Macropinocytosis is the bulk uptake 11 driven by a coat made of the whereas myosin II promotes closure of the cup (FIG. 2). of extracellular medium through large, goblet-shaped protein caveolin. Microtubule motors might contribute to phagosome invaginations; a process that morphologically and formation by delivering endomembranes to the nas- mechanistically resembles phagocytosis. In the fresh- Clathrin- and caveolae- Acanthamoeba independent endocytosis cent phagocytic cup, although the motors that could be water amoeba , the three myosin I isoforms A form (or forms) of uptake involved have not yet been identified. In the amoeba associate with macropinocytic cups in a way that is sim- that is revealed when the two Dictyostelium discoideum, various myosin-I motors have ilar to their association with phagocytic cups21. A similar other endocytosis pathways been localized to the phagocytic cup, and their over- situation has been observed in D. discoideum22 (reviewed are blocked. expression or deletion affects the uptake of particles12 in REF. 13). Class-I myosins are known to associate with Lamellipodia (reviewed in REF. 13). It has recently been proposed, for membranes directly (BOX 2) by binding to acidic phospho- 2+ Sheet-like plasma-membrane both amoeba and yeast, that myosin-I motors function lipids in a Ca -dependent manner, and they probably protrusions that are formed by not in transport per se, but rather in the regulation remain associated through numerous rounds of ATP actin polymerization at the and organization of the actin nucleation–polymeriza- hydrolysis23. Myosin dissociation from phagosomes
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